ABSTRACT: Oligomeric, conjugated water soluble (p-phenylene-ethynes) ("OPEs") are strongly fluorescent at long wavelengths and are "superquenchable" by interaction with appropriate small molecules. They and the polymeric versions ("PPEs"), however, have significant drawbacks as biomolecular probes in aqueous solution. They are long rodlike (bulky) structures and display considerable temperature- and salt concentration-dependence in their fluorescence properties as a result of aggregation in aqueous solutions. We have prepared a minimal length oligomer of this type, a "3.5-mer" [based on three repeating phenylene-ethyne units capped with a phenyl group, i.e. "0.5 unit"], that has significant fluorescence yield and does not show the temperature and salt-dependence of its fluorescence in water. The latter property makes this and related "OPE3.5" oligomers potentially useful as probes for study of biomolecular interactions. We will use an efficient, solid state synthesis approach to prepare a limited family of specific, highly fluorescent oligomers - oligo(p-phenylene-ethyne)s ("OPEs"). The compounds will possess a free carboxyl group at one terminus, enabling them to be covalently attached to biomolecules such as proteins and nucleic acids. In order to assess their potential utility, one oligomer will be conjugated to the drug- binding protein human serum albumin (HSA), and the interaction of the construct with typical drugs will be measured by observing changes in fluorescence, i.e. quenching, as a function of concentration. The specific aims of this project are to: 1. conduct solid state synthesis of four substituted "OPE3.5- mers" containing terminal carboxy groups;2.characterize the fluorescence properties (excitation and emission spectra, quantum yield, potential for aggregation) of the synthesized compounds;3. Activate and covalently attach a selected oligomer to human serum albumin (HSA), and characterize the stoichiometries and fluorescence properties of the products, and 4. Study the effect of interaction with typical albumin-binding drugs on the fluorescence of the HSA-oligomer conjugates. The synthesis and properties of related hydrophobic and hydrophilic, i.e. water soluble, polymers have been reported, but no systematic studies of related oligomers have been reported. Thus, their potential as biomolecular probes is unexplored. The novel oligomers and their reactive derivatives will represent breakthroughs in assay development, and will be offered for sale to companies and research institutions for discovery of new applications of these materials. PUBLIC HEALTH RELEVANCE: NARRATIVE: We will synthesize four specific conjugated, oligomeric compounds, and study their fluorescence properties. The oligomers will be "activated" and one will be attached to an important drug-binding protein - human serum albumin - to test its promise as a sensor to study its interaction with drugs and other small molecules. Such novel oligomers and their reactive derivatives will be offered to companies and research institutions for discovery of new applications of these materials.